This research project is designed to carry out bioassay-directed isolation, structural elucidation, and chemical studies of novel antineoplastic agents from higher plants which have confirmed activity in a panel of human tumors in cell culture. The cell lines which are in place (HT-29, A549, MCF-7, RPMI-7951 and TE671) have been chosen based on consideration of refractory disease-type and overlap with the panel of human tumor cell lines being established by the National Cancer Institute (NCI). Plant materials are obtained through botanical contacts world-wide and from NCI. A large number of plant extracts are on hand with confirmed activity in these systems and/or 9PS. Bioactivity- directed fractionation is underway on Annona species, Canaga oderata, Anomodon species and other mosses including Claopodium crispifolium and polytrichum ohioensis. Structural work and chemical studies are underway on crystalline actives from psorospermum febrifugum, Annona densicoma, A. reticulata, polytrichum ohioensis and others, Compounds with selective activity for the human tumor cells have been discovered and are under study. Selected novel actives will be submitted to the NCI for further evaluation in the NCI human tumor panel and animal models. This research will provide additional novel antineoplastic agents which have clinical potential. Compounds discovered will also serve as structural prototypes for analog synthesis and as biochemical probes which may aid in the elucidation of novel mechanisms of growth control and novel therapeutic targets.